Objectives: To assess 1) the effectiveness of male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury and related mortality; and 2) whether this effect varies across different patient subgroups. Design: Systematic Review and meta-analysis: Data were identified by querying MEDLINE and EMBASE (including proceedings of major conferences on blood transfusions), searching the Internet for hemovigilance reports, reviewing reference lists of eligible articles and contacting experts in the field. Eligible were all studies reporting transfusion-related acute lung injury incidence, allcause mortality (primary outcomes), hospital length of stay, time to extubation, Pa<inf>o2</inf>/F<inf>io2</inf>-ratio or blood pressure changes (secondary outcomes) in recipients of plasma transfusions containing relatively more plasma from individuals at low risk of carrying leukocyte-antibodies ("male plasma") than those receiving comparator plasma ("control plasma"). No limits were placed on study design, population or language. The only exclusion criteria were non-human subjects and lack of control group. Prespecified study quality indicators (including risk of bias assessment) and potential effect modifiers were tested using Cochran's Q Test. Final analyses using random-effects models and I<inf>2</inf> to assess heterogeneity were performed in the subset of studies judged to provide the best evidence and separately for significantly different subgroups using STATA 12.1 (StataCorp, College Station, TX). Setting: As per primary studies. Patients/Subjects: As per primary studies. Interventions: As per primary studies (generally: exposure to plasma containing relatively more male plasma than comparator plasma). Measurements and Main Results: From a total of 850 retrieved records, we identified 45 eligible studies. For transfusion-related acute lung injury incidence, final analysis was restricted to 13 cohort studies and one randomized controlled trial in which transfusion-related acute lung injury cases only involved plasma transfusions. Risk of transfusion-related acute lung injury and mortality in plasma recipients exposed to men when compared with control plasma were 0.27 (95% CI, 0.20-0.38; p < 0.001; I<inf>2</inf> = 0%; n = 14; 286 events) and 0.89 (95% CI, 0.80-1.00; p = 0.04; I<inf>2</inf> = 79%; n = 7; 5, 710 events), respectively. No other significant interactions were found. Secondary outcomes showed similar results but were less reported and the studies were more heterogeneous. Sensitivity analyses did not alter the results. There was no evidence of publication bias. Discussion: More than 800 million people in 17 countries are subject to male-predominant plasma transfusion policy and at least three more countries are planning or considering adoption of this strategy. On the basis of most observational data, judged to be of high quality, male-predominant plasma transfusion strategy reduces plasma-related transfusion-related acute lung injury incidence and possibly mortality. There was no evidence that the effect differs across patient subgroups, but power to detect such differences was low.